Vasculitis Flashcards
(19 cards)
What is Vasculitis?
🔥 What is Vasculitis?
Vasculitis is inflammation of blood vessels — it can affect arteries, veins, or capillaries, but most commonly affects arteries.
⸻
🩸 Key Points:
- What happens in vasculitis?
- The immune system attacks the blood vessel wall.
- This causes inflammation, which can lead to:
- Thickening of the vessel wall
- Narrowing or blockage → ischemia
- Weakening of the wall → aneurysm or rupture
- Types of vessels involved:
- Arteries (most commonly): small, medium, or large
- Capillaries (in small-vessel vasculitis)
- Veins (rarely, but can be involved)
- most cases are not infectious
- symptoms are non-specific (fatigue, fever, weight loss, myalgia)
- symptoms of organ ischemia can occur
Vasculitis = inflammation of blood vessels (mostly arteries), causing tissue damage due to poor blood supply.
How do endothelial cells get damaged and lead to thrombosis?
- endothelial cells get damaged exposing the subendothelial collagen + tissue facors underneath, this activates coagulation cascades and results in the formation of a thrombus –> organ ischemia can occur due to this thrombosis.
- healing of damaged blood vessel can also lead to Fibrosis (narrowing Lumen) and can give ischemia symptoms
What is the classification of vasculitides based on the size of the blood vessels involved?
- Large-Vessel Vasculitis
- Vessels affected: Aorta and its major branches
- Diseases:
- Takayasu Arteritis – “pulseless disease”, young Asian females
- Giant Cell Arteritis (Temporal Arteritis) – elderly, temporal headache, jaw claudication, vision loss
⸻
- Medium-Vessel Vasculitis
- Vessels affected: Muscular arteries that supply organs
- Diseases:
- Polyarteritis Nodosa (PAN) – associated with Hep B, affects renal and visceral vessels, not lungs
- Kawasaki Disease – children, coronary artery aneurysms, strawberry tongue, rash, conjunctivitis
⸻
- Small-Vessel Vasculitis
- Vessels affected: Arterioles, capillaries, venules
- Subtypes:
- ANCA-Associated:
- Microscopic Polyangiitis (p-ANCA)
- Granulomatosis with Polyangiitis – GPA / Wegener (c-ANCA)
- Eosinophilic Granulomatosis with Polyangiitis – EGPA / Churg-Strauss (p-ANCA)
- Immune Complex Mediated:
- IgA Vasculitis – Henoch-Schönlein Purpura (HSP), kids, palpable purpura, abdominal pain
- Cryoglobulinemic Vasculitis – often HCV-related
- Anti-GBM Disease – Goodpasture’s, pulmonary hemorrhage + glomerulonephritis
What is Temporal (Giant Cell) Arteritis?
🧠 What is it?
* Chronic granulomatous inflammation of large arteries (especially branches of the carotid).
- Large vessel vasculitis
** most common form of vasculitis in older adults (> 50 years)
- usually affects females
Treatment is with Corticosteroids because there is a high risk of blindness without treatment
What does Granulamatous vasulities mean?
- Temporal Giant Cell Arteritis is a form of Granulamatous vasculitis
A granulomatous inflammation is a chronic type of inflammation where the body tries to wall off something it can’t easily eliminate — like an infection, a foreign substance, or even damaged tissue.
⸻
🧠 Think of it like:
🔨 “If your immune system can’t destroy it… it builds a wall around it.”
That wall is made up of special immune cells:
* Macrophages (big eaters) that fuse to form:
* Giant cells (lots of macrophages stuck together)
* Surrounded by T cells and fibrosis (scar tissue)
In Giant Cell Arteritis:
* The artery wall gets inflamed with granulomas
* Giant cells are present
* This inflammation narrows the lumen, reducing blood flow —> leading to ischemic symptoms (like vision loss or jaw pain)
Giant Cell Arteritis (GCA), also known as Temporal Arteritis — a granulomatous large-vessel vasculitis has what symptoms?
🔴 Affected Vessels:
* Aorta and major branches
* Especially the external carotid artery and its branches like the superficial temporal artery
🧠 Symptoms:
* Raised & tender temporal artery
* Jaw claudication (pain when chewing)
* Vision loss — due to ischemia of the ophthalmic artery
* Neck/jaw pain, tongue necrosis (rare)
* Fatigue, fever, weight loss → systemic inflammation
📌 Patient Profile:
* Age: > 55 years
* More common in women
* Nordic ancestry (increased prevalence)
* Strongly associated with Polymyalgia Rheumatica
⚠️ Complications:
* Aortic aneurysm
* Stroke
* Irreversible blindness if untreated
⸻
📚 Clinical Point:
Giant Cell Arteritis is an emergency when it involves the ophthalmic artery — immediate treatment with high-dose corticosteroids is crucial to prevent permanent vision loss.
- Targets external carotid artery branches, mainly temporal artery → causes headache, vision loss, and jaw claudication.
What is Takayasu Arteritis?
- a form of Granulomatous vasculitis with Giant Cells
- presents in adults < 50 years old
- young asian females affected
- “Pulseless disease” → Young women, no pulse in upper limbs
- involves proximal aorta + major branches, especially subclavian, carotid, and renal arteries → causes pulselessness, hypertension, limb ischemia.
What is Polyarteritis Nodosa?
- it is a form of necrotizing Medium Vessel vasculitis
- involves multiple organs
** Lungs are spared - associated with serum HBsAg (Hep. B surface antigen)
🔥 1. Lesions of Varying Stages
This means that:
* In the same patient (even in the same artery), you can find acute, healing, and healed areas of vasculitis.
* This is unique to PAN and helps distinguish it from some other vasculitides, which tend to show uniform stage of involvement.
💡 Why it matters:
* It reflects ongoing, wave-like attacks on vessels over time — some vessels are freshly inflamed, some are scarred.
⸻
🌊 2. ‘String-of-Pearls’ Appearance on Imaging
Seen on angiography (e.g., mesenteric or renal arteriography):
* Microaneurysms appear as small outpouchings (the “pearls”).
* Narrowings between them are due to inflamed or occluded vessel segments (the “string”).
* Together, this produces a beaded or “string-of-pearls” look.
🧠 What causes this?
* Transmural necrotizing inflammation weakens the arterial wall → leads to aneurysms.
* Ongoing inflammation and thrombosis narrow other segments.
** treatment is corticosteroids and cyclophosphamide. Fatal if not treated
What does a Histo slide of Polyarteritis Nodosa look like?
- pink due to Fibrinoid Necrosis
What is Kawasaki Disease?
- clinically affects Asian children < 4 years old
Presentation: fever, conjuctivitis, strawberry tongue, errythematous rash of palms and soles of feet, enlarged cervical lymph nodes (non-specific symptoms)
- coronary artery involvement is common
- Kawasaki Disease (KD) is an acute, febrile vasculitis that affects medium-sized arteries, especially the coronary arteries, and occurs primarily in children under 5 years old.
❤️ Why It Matters: Cardiac Involvement
The most dangerous complication is coronary artery aneurysm, which can lead to:
* Myocardial infarction
* Sudden death
📍 Key Points
* Age group: mostly < 5 years
* Risk of coronary aneurysms if untreated
* NOT responsive to antibiotics (not a typical bacterial infection)
Labs: ↑ ESR, ↑ CRP, leukocytosis, thrombocytosis (after 2nd week), sterile pyuria
Treatment: use aspirin (one of the only times you give aspirin to children, Anti-inflammatory and anti-platelet (rare case where aspirin is used in children)
) and IVIG (intravenous immunoglobulin) which reduces risk of coronary aneurysm (start within 10 days of fever)
How does Aspirin work for Kawasaki Disease?
🔬 Aspirin: Mechanism of Action
Aspirin is an NSAID (nonsteroidal anti-inflammatory drug) that works by irreversibly inhibiting the enzymes:
* COX-1 (Cyclooxygenase-1)
* COX-2 (Cyclooxygenase-2)
These enzymes convert arachidonic acid → prostaglandins and thromboxanes, which mediate inflammation, pain, fever, and platelet aggregation.
⸻
🧪 How Aspirin Helps in Kawasaki Disease:
🩺 1. Anti-inflammatory Effect (High-dose Aspirin)
* In the acute phase of Kawasaki disease, inflammation is very high.
* Aspirin inhibits COX-2, decreasing prostaglandins (PGE2 especially), which:
* Lowers fever
* Reduces inflammation and swelling
🗓 Given during the acute febrile stage (high dose).
⸻
🩸 2. Anti-platelet Effect (Low-dose Aspirin)
* After the fever resolves (subacute/chronic phase), aspirin is continued at a low dose.
* This is because coronary aneurysms can form, increasing the risk of thrombosis (blood clots) in the damaged vessels.
🔬 Mechanism:
* Aspirin irreversibly inhibits COX-1 in platelets → ↓ Thromboxane A2 → ↓ Platelet aggregation.
🗓 Continued for weeks to months to reduce risk of heart attack/stroke.
⸻
💡 Why is Aspirin Unique?
* It’s the only NSAID that irreversibly inhibits COX.
* Other NSAIDs (like ibuprofen) do it reversibly.
* This makes aspirin especially effective as an anti-platelet agent.
⸻
🚸 Note on Safety:
* Aspirin is usually avoided in children due to the risk of Reye’s syndrome (a rare but serious condition).
* But Kawasaki Disease is the one exception — the benefits outweigh the risks, especially when combined with IVIG, which seems to reduce Reye’s risk further.
What is Buerger Disease?
- it is a necrotizing vasculitis involving the digits
- presents with ulceration, gangrene, and autoamputation of fingers and toes
- Raynaud’s phenomenon is often present (vasospasms)
- In this disease, blood vessels become inflamed, swell, and can become blokced with blood clots (thrombi)
** highly associated with smoking (smoking cessation is a treatment)
What is Granulomatosis with Polyangiitis (GPA) — formerly known as Wegener’s Granulomatosis?
- are autoimmune small- to medium-vessel vasculitis that causes granulomatous inflammation and necrotizing vasculitis, typically affecting:
- Upper respiratory tract
- Lungs
- Kidneys
🧠 Classic Triad: most present in middle-afed males
1. ENT (Upper respiratory tract) involvement:
* Chronic sinusitis, nasal crusting
* Nasal septal perforation → saddle-nose deformity
* Otitis media, mastoiditis
- palatal destruction
2. Lung involvement:
* Cough, hemoptysis with bilateral nodular lung infiltrates, chest pain, dyspnea
* Cavitary lung nodules (necrotizing granulomas)
3. Renal involvement:
* Rapidly progressive glomerulonephritis (RPGN)
* Hematuria, proteinuria, red cell casts
* Can lead to renal failure
- c-ANCA: Positive (highly specific for GPA)
Treatment: Cyclophosphamide and steroids.
relapses are common.
What Are ANCAs?
ANCAs (Anti-Neutrophil Cytoplasmic Antibodies) are autoantibodies that mistakenly target proteins inside neutrophils (a type of white blood cell). These antibodies are implicated in autoimmune vasculitis, where they trigger inflammation of blood vessels.
There are two main types based on how they stain neutrophils under immunofluorescence microscopy:
⸻
🔬 c-ANCA (Cytoplasmic-ANCA)
* Pattern: Diffuse, granular staining of the cytoplasm of neutrophils
* Main target antigen: Proteinase 3 (PR3) — an enzyme in neutrophil granules
Associated Disease:
* Granulomatosis with Polyangiitis (GPA / Wegener’s)
⸻
🔬 p-ANCA (Perinuclear-ANCA)
* Pattern: Perinuclear staining (around the nucleus)
* Main target antigen: Myeloperoxidase (MPO) — another enzyme in neutrophil granules
Associated Diseases:
* Microscopic Polyangiitis (MPA)
* Eosinophilic Granulomatosis with Polyangiitis (EGPA / Churg-Strauss)
* Also sometimes seen in:
* Ulcerative colitis
* Primary sclerosing cholangitis
⸻
⚙️ How Do They Form?
1. Neutrophil activation or death (due to infection, trauma, etc.) leads to the release or exposure of cytoplasmic proteins like PR3 or MPO.
2. In some genetically predisposed individuals, the immune system misidentifies these proteins as foreign and forms autoantibodies.
3. These ANCAs bind to neutrophils, activating them inappropriately.
4. Activated neutrophils then:
* Stick to vessel walls
* Release ROS (reactive oxygen species) and enzymes
* Damage endothelial cells → vasculitis
⸻
🧠 Analogy:
Imagine neutrophils as “SWAT team members” carrying protein grenades (PR3, MPO). Normally, they only release them on command.
But in ANCA vasculitis:
* Your immune system accidentally pulls the pin on those grenades
* Neutrophils go rogue
* Start attacking your own blood vessels
What is Microscopic Polyangiitis (MPA)?
a small-vessel necrotizing vasculitis that primarily affects the lungs and kidneys, and is p-ANCA positive.
✅ Key Features of Microscopic Polyangiitis:
⸻
🧬 Pathogenesis:
* Immune-mediated necrotizing inflammation of small vessels (capillaries, venules, arterioles).
* p-ANCA (MPO-ANCA) positivity is typical and correlates with disease activity.
⸻
🧑⚕️ Clinical Presentation:
* Lung involvement:
* Hemoptysis due to pulmonary capillaritis → can be life-threatening. This means coughing up blood from the lower respiratory tract — usually from the lungs or bronchi.
* Kidney involvement:
* Rapidly progressive glomerulonephritis (RPGN) → hematuria, proteinuria, renal failure.
* Skin: Palpable purpura. This refers to small, raised (palpable) areas of bleeding under the skin, usually appearing as red or purple spots that do not blanch (fade) when pressed. It’s a classic sign of cutaneous small-vessel vasculitis.
* GI tract: Abdominal pain, bleeding.
* Musculoskeletal: Myalgias, arthralgias, weakness.
* No granulomas (unlike granulomatosis with polyangiitis).
* No nasopharyngeal involvement (a key distinction from GPA/Wegener’s).
⸻
🔬 Diagnosis:
* p-ANCA (anti-MPO) serology.
* Biopsy (kidney/skin): shows necrotizing vasculitis without granulomas.
⸻
💊 Treatment:
* Induction: Cyclophosphamide + corticosteroids.
What are differences between GPA and MPA?
✅ 1. Granulomas:
The most fundamental difference is that GPA forms granulomas, while MPA does not.
* GPA involves necrotizing granulomatous inflammation — structured clusters of immune cells seen on biopsy.
* MPA lacks granulomas; it causes necrotizing vasculitis only.
⸻
✅ 2. Upper Respiratory Involvement:
GPA characteristically affects the upper airways (nasopharynx, sinuses, ears):
* Symptoms like chronic sinusitis, bloody nasal discharge, saddle-nose deformity, and otitis media are classic for GPA.
* MPA spares the upper respiratory tract — so these signs are absent.
⸻
✅ 3. ANCA Type:
Both are ANCA-associated vasculitides, but the type of ANCA differs:
* GPA: Usually c-ANCA (anti-PR3).
* MPA: Usually p-ANCA (anti-MPO).
* This helps differentiate them serologically, though there’s some overlap.
⸻
✅ 4. Histology:
* GPA biopsy: Shows granulomatous inflammation, necrosis, and vasculitis.
* MPA biopsy: Shows necrotizing vasculitis without granulomas.
⸻
✅ 5. Lung and Kidney Involvement:
Both can affect the lungs and kidneys:
* Lungs:
* GPA: Lung nodules, cavitations, or infiltrates due to granulomas.
* MPA: Diffuse alveolar hemorrhage is more prominent due to capillaritis.
* Kidneys:
* Both can cause rapidly progressive glomerulonephritis (RPGN), presenting with hematuria and proteinuria.
⸻
✅ 6. Demographics & Course:
* GPA may present more gradually with chronic sinus/ENT symptoms before lung/kidney disease appears.
* MPA often presents more acutely with systemic signs like fever, purpura, hemoptysis, and glomerulonephritis.
What is Eosinophilic granulomatosis with Polyangiitis (EGPA)? – formerly known as Churg Strauss syndrome
🦠 What is EGPA?
EGPA (formerly Churg-Strauss syndrome) is a rare disease where the immune system attacks small and medium blood vessels, causing inflammation.
It mostly affects people with asthma and high levels of eosinophils (a type of white blood cell).
⸻
🧬 Key Features:
- Asthma
- Almost always present
- Usually severe and long-standing
- Eosinophilia
- High eosinophil count in the blood
- Also seen in tissues (especially lungs)
- Vasculitis
- Inflammation of blood vessels
- Causes organ damage especially in lungs and hear, can involve skin and nerves
⸻
🔬 What Does a Biopsy Show?
* Granulomas: Clumps of immune cells
* Eosinophilic debris in the center (dead eosinophils)
* Surrounded by histiocytes and more eosinophils
* Also shows necrotizing (damaging) inflammation
⸻
🧪 Lab Tests:
* p-ANCA positive in ~40–60% of patients
* High eosinophil count
What is Immunoglobulin A vasculitis (IgA vasculitis) — formerly called Henoch-Schönlein Purpura (HSP)?
- It is mall-vessel vasculitis caused by IgA immune complex deposition in vessel walls.
- ** most common Vasculitis in children
- ** usually occurs following an upper respiratory tract infection
⸻
🧬 What is it?
* It’s an immune reaction where IgA antibodies form complexes that get stuck in small blood vessels, causing inflammation.
* Most common vasculitis in children, but can affect adults too.
⸻
🩸 Key Features:
* Palpable purpura (raised purple spots) usually on the lower legs and buttocks
* Arthritis/arthralgia (joint pain, especially knees and ankles)
* Abdominal pain (due to GI tract vasculitis, sometimes with bleeding)
* Kidney involvement: IgA deposits cause glomerulonephritis, leading to blood/protein in urine
⸻
🔬 Pathology:
* Blood vessel walls show IgA deposits on immunofluorescence.
* Vasculitis is mostly in capillaries, venules, and small arterioles.
⸻
🎯 Clinical Course:
* Usually self-limited in kids, with good prognosis.
* Adults can have more severe kidney problems.
⸻
💊 Treatment:
* Mainly supportive: hydration, pain control.
* Severe cases (especially kidney involvement) may need steroids or immunosuppressants.
What is Behcets Disease?
🦠 What is it?
A vasculitis (inflammation of blood vessels) that mainly affects mucous membranes across many organs. (Inflammation throughout the body)
⸻
🔑 Main Clinical Features:
* Recurring oral ulcers (painful, often multiple)
* Genital ulcers (similar to oral ulcers, often painful)
* Eye inflammation:
* Uveitis (inflammation of the middle layer of the eye)
* Iritis (inflammation of the iris)
* Can also involve other systems:
* Gastrointestinal tract (pain, ulcers)
* Lungs
* Central nervous system (CNS)
* May cause vascular aneurysms (dangerous vessel bulges)
⸻
🧬 Genetics:
* Strong association with HLA-B51 gene.
⸻
💊 Treatment:
* Steroids to reduce inflammation
* Mouthwash to relieve oral ulcers
* Eye drops for eye inflammation
* Immunosuppressants or biologics may be needed in severe cases.
⸻
📝 Summary:
Behçet’s Disease causes recurring painful ulcers in the mouth and genitals, eye inflammation, and can affect many organs due to blood vessel inflammation. It’s linked to a genetic marker called HLA-B51.
